tbuckley/cabot-search huggingface dataset:
P1494: EFFECT OF IRON DEFICIENCY ANEMIA ON PROPRIOCEPTION IN ADULT WOMEN
Authors: Ines Mezghani, Achraf Harrabi, Rahma Ayed, Mouna Turki, Sonia Sahli, Fatma Ayadi
Journal: HemaSphere (2023)

Topic: 29. Iron metabolism, deficiency and overload Background: According to the World Health Organization (WHO), one-third of the world’s population was affected by anemia. The most common cause of anemia is iron deficiency. Due to menstruation and restrictive dietary practices, women are at a particular risk of iron deficiency anemia. Proprioception is essential to several conscious and unconscious sensations and automatic control of movement in daily life activities. Iron deficiency anemia (IDA) may alter proprioception as it could induce fatigue, and affect neural processes such as myelination, and neurotransmitters synthesis and degradation. Aims: The aim of our study was to explore the effect of IDA on proprioception in adult women. Methods: This case–control study was conducted with 30 adult women with IDA and 30 healthy controls matched in age, weight, height, and body mass index. The weight discrimination procedure was used to measure the proprioceptive acuity. Attentional capacity and fatigue were evaluated, too. The statistical analyses were carried out using the statistical software program, IBM® SPSS® Statistics version 25.0, for Windows. Results: Women with IDA had a significantly (P < 0.001) lower ability to discriminate weights compared to controls in the two difficult increments, and for the second easy weight (P < 0.01). For the heaviest weight, no significant difference was found. Attentional capacity and fatigue values were significantly (P < 0.001) higher in patients with IDA compared to controls. Besides, moderate positive correlations between the representative proprioceptive acuity values and Hb (r = 0.68) and ferritin (r = 0.69) concentrations were found. Moderate negative correlations were found between the proprioceptive acuity values and general (r = − 0.52), physical (r = − 0.65) and mental (r = − 0.46) fatigue scores, and attentional capacity (r = − 0.52). Summary/Conclusion: This study revealed that IDA induces proprioceptive deficits in adult women. Hemoglobin and ferritin concentrations decrease, poor attentional capacities, and physical fatigue, as well as general and mental fatigue, could explain this proprioceptive deficit considering the correlations found between them. Clinicians should be aware of the proprioceptive deficit in women with IDA and take it into consideration in treatment strategies. Keywords: Female, Adult, Iron deficiency anemia, Anemia
P1503: ETIOPATHOGENESIS OF CANCER-RELATED ANEMIA AMONG CHILDREN AND ADOLESCENTS WITH MALIGNANT SOLID TUMORS
Authors: Salwa Mostafa Abd El Kader Kader, Menna Allah Zakaria Mohammad Ali Abouelwafa, Aya Tallah Ibrahim Abdel Aleim, Iman Ragab
Journal: HemaSphere (2023)

Topic: 29. Iron metabolism, deficiency and overload Background: Anemia in cancer patients is a common comorbidity at diagnosis and throughout treatment, which does not appear to be a consequence of concurrent antineoplastic therapy; rather than being multifactorial. Anorexia, Malnutrition and lack of specific components (such as iron, vitamins, folic acid, etc.) fundamental for erythropoiesis contribute to the multifactorial pathogenesis of anemia. Caner related anemia (CRA) is primarily caused by the chronic inflammation associated with the cancer pathogenesis, as cancer cells mediate the activation of immune cells particularly the macrophages increasing the secretion of interleukin 6 (IL-6) among other inflammatory mediators contributing to CRA. Aims: To evaluate IL 6 levels among children and adolescents presenting with suspected solid tumors induced CRA, as well as recognition of iron status and other possible causes of anemia in pediatric malignant solid tumors. Methods: A 6 months cross sectional study included 30 patients with solid tumors and anemia following at hematology/oncology clinic, Ain Shams University. Detailed review of the patient’s clinical and laboratory data of disease diagnosis, stage at diagnosis, daily iron intake, bone marrow biopsy results, and IL6 assay by ELISA, as well as serum ferritin, transferrin saturation index (TSI) were done upon anemia presentation. Results: Thirty patients with Solid Tumors were recruited with median (IQR) age of 6(2.5-10) years at presentation, 26.7 % (n=8) diagnosed with brain tumors and 23.3 %(n=7) with neuroblastoma. The mean±SD hemoglobin was 9.21±1.33, among which 80% (n=24) showed inadequate 24 hrs iron intake. Nineteen patients (63.3%) had functional iron deficiency anemia, while 36.7% (n=11) had combined true and functional iron deficiency anemia. IL 6 median (IQR) level =88.6 (57.5-156.5), which showed no statistical significant difference (p=0.561) among patients with true and functional iron deficiency. Summary/Conclusion: Anemia among cancer patient’s can be multifactorial with some of patient’s experiencing true iron deficiency anemia that can be managed by proper dietetic iron supplementation, Yet CRA represents as state of chronic inflammation with functional iron deficiency that needs proper recognition. Keywords: Cancer, Anemia
PB2612: UNITED KINGDOM RETROSPECTIVE OBSERVATIONAL STUDY OF ROMIPLOSTIM AND OTHER TREATMENTS IN EARLY IMMUNE THROMBOCYTOPENIA
Authors: Vickie Mcdonald, Charlotte Bradbury, Kate Talks, Gillian Lowe, Sue Pavord, Gillian Evans, Mano Andiappan, Darcie Sandschafer, Vitor Jose De Sousa Barbosa, Lorraine Stephens, Nichola Cooper
Journal: HemaSphere (2023)

Topic: 32. Platelet disorders Background: As of 2021, the thrombopoietin receptor agonist (TPO-RA) romiplostim is licensed for adults with immune thrombocytopenia (ITP) across all disease phases, including duration ≤1 year refractory to first-line treatments. While aligned with treatment guidelines, real-world UK data on this indication are lacking. Aims: To assess the response to romiplostim, we performed a retrospective UK-wide study of real-world treatment patterns in adults with primary ITP ≤1 year from diagnosis between 2 July 2015 and 23 March 2020. Methods: Recruited patients were divided into those who either did (Group 1) or did not (Group 2) receive romiplostim during the first year from diagnosis. TPO-RAs, including eltrombopag, could be received in either group after the first year (excluding eltrombopag in the first year). All efficacy and safety analyses were descriptive. Results: Seventy-eight patients enrolled at seven UK sites; Group 1 (n=13) 62% female, median (min-max) platelets 4 (2-44)×109/L and Group 2 (n=65) 59% female, median (min-max) platelets 7 (0-108)×109/L (Table). In Group 1, romiplostim was initiated (off-license) at a median of 6 weeks with a median treatment duration of 63 weeks; 2/13 received romiplostim first-line and 11/13 as the second treatment or later. Romiplostim treatment continued in 8/13 patients at study end. Other treatments in Group 1 in more than one patient included: prednisolone (n=11), mycophenolate mofetil (MMF, n=5), IVIg (n=4), and rituximab (n=3). In Group 2, two patients (3%) received no treatment; 33 patients (51%) received corticosteroids ± IVIg ± tranexamic acid only without further escalation; 26 patients (40%) required MMF or rituximab. In the second year, six patients (9%) in Group 2 required a TPO-RA. The median treatment duration was shorter for Group 1 vs 2 for prednisolone (3 vs 10 weeks for those discontinuing prednisolone) and MMF (13 vs 39 weeks). By the end of the 2-year treatment period, median (interquartile range) platelet counts had increased to 157 (81-275) and 122 (81-202)×109/L in Groups 1 and 2, respectively. During the observation period in Groups 1 and 2, respectively, bleeding episodes occurred in 54% and 63% of patients, and rescue therapies were required by 39% and 31% of patients. The mean number of rescue therapies/patient was 0.6 and 0.8 in Groups 1 and 2, respectively. Thromboembolic events occurred in one patient in each group (Group 1: sub-acute left lower limb arterial ischemia; Group 2: stroke).Summary/Conclusion: These findings support further exploring the earlier use of romiplostim for adult patients with primary ITP. Keywords: Immune thrombocytopenia (ITP), Thrombopoietin (TPO), Thrombocytopenia, Platelet
PB2316: SAFETY AND EFFICACY OF AUTOLOGOUS HSCT IN NINE PATIENTS WITH AIDS-RELATED NON-HODGKIN LYMPHOMA
Authors: Jun Liu, Yixing Zhou, Shunsi Liang, Chensi Zeng, Dehong Huang, Chunyan Xiao, Tao Yang, Jieping LI, Yingyu Nan, Qiying LI, Ying Xiang, Yao Liu
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: In recent years, with the application of HIV combined with resistance retroviral therapy, the number of AIDS-NHL patients has gradually increased, surpassing Kaposi’s sarcoma and becoming the first AIDS-related tumor. The prognosis of AIDS-NHL patients is worse than that of ordinary NHL patients, and more powerful treatment is needed. Aims: To analyze the safety and efficacy of 9 AIDS-related non-Hodgkin lymphoma (AIDS-related non-Hodgkin lymphoma, AIDS-NHL) treated with autologous hematopoietic stem cell transplantation (auto-hematopoietic stem cell transplantation, ASCT). Methods: 9 patients with AIDS-NHL were prospectively treated for their safety and efficacy. Results: The male to female ratio of 9 AIDS-NHL patients was 8:1, and the median age was 38 years. The pathology types were 4 DLBCL, 2 PBL, 1 BL, 1 HGBL and 1 HL, including 3 patients with refractory relapse (1 each of DLBCL, HGBL and PBL). Except for three patients with refractory relapse, the remaining six patients underwent first-line autologous HSCT. One PBL stage was in stage I low-risk group and the remaining patients were in stage III – IV high-risk group. Before transplantation, one patient was progressive, one patient was in partial remission, and the other patients achieved complete remission after chemotherapy. All patients underwent autologous HSC mobilization using PEG-G-CSF, with all CD34 + cell numbers> 210 ^ 6/ Kg. Transplantation pretreatment was performed with the BeEAM protocol, with a median time to granulocyte engraftment of 11 days and a median time to platelet engraftment of 14 days, with no transplant-related death. Two patients who did not achieve CR before transplantation all died due to disease progression within 3 months after transplantation, and the remaining patients remained in complete disease remission through follow-up until February 28,2023. Summary/Conclusion: AIDS-NHL patients are aggressive and have a poor prognosis, and active treatment is needed to improve their long-term survival. Our center prospectively performed autologous HSCT in nine patients with AIDS-NHL, and the results showed that the time of granulocyte and platelet engraftment was consistent with that of ordinary NHL patients, with no transplant-related death and was well tolerated. Failure to achieve complete remission before transplantation may be one of the adverse factors for the early death of patients.Keywords: AIDS/HIV
PB2389: DIAGNOSTIC SIGNIFICANCE OF CYTOKINE EXPRESSION LEVELS IN CEREBROSPINAL FLUID FOR CENTRAL NERVOUS SYSTEM INFILTRATION OF LYMPHOMA
Authors: Luo Xin, Peng Yu, Chen Shuang, Zhao Mingyu, Ran Longrong, Yang Zailin, Liu Yao
Journal: HemaSphere (2023)

Topic: 20. Lymphoma Biology & Translational Research Background: Central nervous system lymphoma (CNSL) refers to lymphoma of the central nervous system, including brain, spinal cord, pia, and eye. However, the diagnosis, especially the early diagnosis, is difficult, staging, prevention and treatment have not reached consensus, and the survival time is short. Therefore, it is hoped to find serological markers conducive to early clinical diagnosis and differential diagnosis. Some cytokine secretion disorders can promote the growth of tumor cells, play a key role in lymphocyte growth, differentiation and maturation, and participate in immune regulation, tumor occurrence and growth. This study investigated the expression level and clinical value of cytokines in cerebrospinal fluid of patients. Aims: To explore the diagnostic value of cytokine expression level in cerebrospinal fluid (CSF) for central nervous system infiltration of lymphoma. Methods: CSF was collected from 11 patients with CNSL, 45 patients with high risk of lymphoma central nervous infiltration, and 24 patients with other central nervous system (CNS) diseases between October 2021 and February 2023. Cytokine levels were detected by flow cytometry (FCM). Results: The expression levels of TNF-α, TNF-β, INF-γ, IL-17A, IL-4, IL-2, IL-6 and IL-10 in CSF of patients with CNSL were higher than those of patients with high risk of lymphoma central nervous infiltration (P < 0.05). The levels of TNF-β, IL-17A, IL-17F, IL-4 and IL-10 in CSF of patients with CNSL were higher than those of patients with other CNS diseases (P < 0. 05). The levels of TNF-α, IL-8 and IL-6 in CSF of patients with high risk of lymphoma central nervous infiltration were lower than those of other CNS diseases patients, while the levels of IL-10/IL-6 were higher than those of other CNS diseases patients (P < 0. 05). Summary/Conclusion: The expression levels of TNF-β, IL-17A, IL-17F, IL-4 and IL-10 in CSF of patients with CNSL can be used as differential markers for auxiliary diagnosis. The expression levels of TNF-α, TNF-β, INF-γ, IL-17A, IL-4, IL-2, IL-6 and IL-10 in CSF of patients at high risk of lymphoma central nervous infiltration can be used as auxiliary indicators to predict the risk of lymphoma central nervous infiltration. Keywords: CNS lymphoma, Cytokine, Diagnosis
P1475: MUTATIONS IN THE GAP DOMAIN OF RACGAP1 CAUSE DEVELOPMENTAL AND ERYTHROID DEFECTS IN ZEBRAFISH
Authors: Lídia Romero-Cortadellas, Aitor Bañón, Gonzalo Hernández, Santiago Pérez-Montero, Cristian Tornador, Berta Alsina, Mayka Sanchez
Journal: HemaSphere (2023)

Topic: 28. Enzymopathies, membranopathies and other anemias Background: We recently reported that RACGAP1 mutations are responsible for Congenital Dyserythropoietic Anemia (CDA) type IIIb, a rare autosomal recessive disease characterized by macrocytic anemia and giant multinucleated erythroblasts in the bone marrow. So far, three RACGAP1 mutations have been identified causing CDA IIIb in humans: Thr220Ala, Leu396Gln and Pro432Ser, the two latter affecting the GAP domain. It was previously described that complete abrogation of Racgap1 in Danio rerio (zebrafish) shows defects in cytokinesis and erythropoiesis with an anemic phenotype (ogre mutant). The effect of specific point mutations in the Racgap1 gene in zebrafish is not known. Aims: We generated two Racgap1 knock-in zebrafish models within its GAP domain (Pro415Ser and Pro440Ser, equivalent to human Pro407Ser and Pro432Ser, respectively) to study the pathogenicity of these variants in animal models. Methods: The knock-in mutants were generated with CRISPR technology. Single-cell zebrafish embryos were injected with protein Cas9, a dgRNA to generate a double-strand break and a ssODN for homologous recombination. Fish were allowed to grow for 3 months before screening experiments to identify the mutants. F1 heterozygous fish were crossed and the offspring was analyzed for developmental and erythroid defects. Results: The zebrafish Racgap1 Pro440Ser mutant is lethal, as shown by a negative selection of mutated fish. The homozygous zebrafish Racgap1 Pro415Ser mutant is viable; however, mutated zebrafish show development impairment and erythroid defects with a 10% of surviving individuals presenting a bloodless phenotype. Summary/Conclusion: Racgap1 mutations within the GAP domain in zebrafish are key for an appropriate global development and particularly for erythropoiesis. These results further confirm the pathogenicity of these variants in the erythroid context by D.rerio as an animal model.Left panels: WT zebrafish morphology (top) and of their circulating erythrocytes (bottom). Right panels: homozygous Racgap1 Pro415Ser zebrafish morphology (top) and of their circulating erythrocytes (bottom). Keywords: Anemia, Gene mutation, Zebra fish, Erythroid
P1229: PARP INHIBITORS ARE EFFECTIVE IN NATURAL KILLER/T CELL LYMPHOMA VIA THE EXPRESSION OF LMO2
Authors: Jiazhuo Wu, Mingzhi Zhang
Journal: HemaSphere (2023)

Topic: 31. Transfusion medicine Background: PARP inhibitors (PARPis), as a kind of DNA damage repair inhibitor, have been shown to be effective in various solid tumors and hematologic malignancies. Natural killer/T cell lymphoma (NKTCL) is a highly aggressive malignancy, the treatment of which has long been a major challenge in the clinic. Here, we explored the efficacy of PARPis in NKTCL cells, as well as their associated mechanism. Aims: In our study, we explored the efficacy of PARPis in NKTCL cells, as well as their associated mechanism. Methods: The cell proliferation, cell apoptosis and cell cycle of NKTCL cells were detected respectively by CCK-8 and flow cytometry. The changes of mRNA expression and protein level were measured respectively by mRNA-seq, quantitative RT-PCR, western blotting and immunofluorescence. LMO2 expression was detected by immunohistochemistry and western blotting. Targeted knockdown of LMO2 was conducted by short hairpin RNA. The tumor xenograft models were established to evaluate the efficacy of drugs in vivo. Results: NKTCL cells were sensitive to PARPis, showing decreased cell proliferation, increased cell apoptosis and S-phase cell cycle arrest. Furthermore, fluzoparib, one of the PARPis, caused the accumulation of DNA damage, and LMO2 deficiency reduced the sensitivity of NKTCL cells to PARPis. Additionally, NKTCL patients with high LMO2 expression may have better progression-free survival and overall survival. Finally, the combination of fluzoparib and cisplatin exhibited significant synergistic effects both in vitro and in vivo. Summary/Conclusion: In summary, we found that PARPis exerted an anti-lymphoma effect in NKTCL, and the underlying mechanisms may be “synthetic lethality-like” via LMO2 expression. Moreover, LMO2 may be a novel indicator for drug sensitivity and prognosis in NKTCL. These findings offer a foundation for the clinical application of PARPis and provide certain implications for the clinical management of NKTCL. Keywords: DNA repair
PB2400: THE EFFECT OF BONE MARROW CD4/CD8+ RATIO ON RESPONSE TO TREATMENT AND SURVIVAL IN LYMPHOMAS
Authors: Vahit Can Cavdar, Istemi Serin, Osman Yokus
Journal: HemaSphere (2023)

Topic: 20. Lymphoma Biology & Translational Research Background: T cells can be divided into two subgroups as CD4+ T helper and cytotoxic T cells. Regulatory T cells (Tregs) make up a small group of CD4+ T cells. Tregs have been shown to induce tumor progression and inhibit the antitumoral immune response. While CD8+ T cells produce a variety of cytokines, their main activity is to eliminate infected host cells. Aims: In our study, we aimed to examine the effects of CD4/CD8 ratio on treatment response and survival in newly diagnosed lymphoma patients in samples obtained from bone marrow aspirates at the time of diagnosis. Methods: Patients diagnosed with lymphoma (Hodgkin and non-Hodgkin (HL, NHL) at Istanbul Training and Research Hospital, Hematology Clinic between January 2010 and January 2021 and whose flow cytometric analysis was performed by bone marrow aspiration at the time of diagnosis were included in this study. Results: A total of 126 patients were included in the study. In the statistical analysis performed to show the effect of CD4/CD8 ratio on the interim response, it was observed that the ratio was significantly higher in those who had complete response in the interim evaluation compared to the other subgroup (p<0.05). In the statistical analysis performed to show the effect of the ratio on the end-of-treatment response, it was found that the mean CD4/CD8 ratio was higher in patients with a complete response (CR) compared to those with a non-CR (p=0.008). The sensitivity of the CD4/CD8 ratio was 35.29%, and the specificity was 89.47% for the cut-off of ≤0.38 in terms of end-of-treatment (response other than CR). The sensitivity of the ratio was calculated as 79.17% and the specificity as 54.46% for the cut-off of ≤0.87 in terms of end-of-treatment when grouped as partial responders and others. No significant results were obtained in the survival analysis. Summary/Conclusion: Our study includes both HL and NHL patients, and contains important data for future literature, with the ratios studied from a difficult “hard-to-obtain” sample such as bone marrow. It has been demonstrated that a high CD4/8 ratio in the bone marrow contributes positively to the treatment response of lymphomas.Keywords: Hodgkin’s lymphoma, B cell lymphoma, CD8 T cells, CD4+ T cells
P1561: HBSAG-POSITIVE PATIENTS WITH CO-REACTIVATION OF CYTOMEGALOVIRUS AND EPSTEIN-BARR VIRUSES AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION ASSOCIATED WITH POOR SURVIVAL
Authors: Jinhua Ren, Jingjing Xu, Dabin Chen, Jianda Hu, Ting Yang
Journal: HemaSphere (2023)
P1000: JUVENILE MYELOMONOCYTIC LEUKEMIA (JMML) INHIBITS T CELL PROLIFERATION VIA THE ECTONUCLEOTIDASE CD39 AND THE PURINERGIC NETWORK
Authors: Jovana Rajak, Naile Koleci, Andreea Mesesan, Christian Flotho, Charlotte Niemeyer, Bertram Bengsch, Miriam Erlacher
Journal: HemaSphere (2023)

Topic: 15. Myeloproliferative neoplasms - Biology & Translational Research Background: Juvenile myelomonocytic leukemia (JMML) is a rare and highly aggressive myeloid neoplasia of early childhood. Due to excessive proliferation and organ infiltration of monocytic and granulocytic progenitor cells, patients are experiencing massive hepatosplenomegaly, respiratory distress, diarrhea and skin rash. JMML is driven by constitutive activation of the RAS signaling pathway induced by mutations in PTPN11 (coding for SHP2), KRAS, NRAS, NF1 and CBL. For most patients, the only curative treatment is hematopoietic stem cell transplantation (HSCT), and Graft versus Leukemia (GvL) effects were shown to be relevant for cure. Especially for patients with PTPN11 mutation, risk of relapse after HSCT remains high. Aims: We hypothesized that relapse after HSCT is caused by immune escape mechanisms allowing JMML cells to circumvent immune control. Methods: We focused on the most aggressive, i.e. PTPN11-mutated JMML subtype and used human naïve JMML cells as well as a genetically modified mouse model expressing Ptpn11D61Y in the hematopoietic system (mx-cre;Ptpn11D61Y/+). Results: Phenotypical analysis of immune escape molecules expressed by naïve JMML cells using mass cytometry revealed strong expression of various immunoregulatory molecules on leukemic myeloid cells, including CD39, CD47, Siglec7, Siglec9, NOX2 and PD-L1. In line with this finding, splenic monocytes and granulocytes of mx-cre;Ptpn11D61Y/+ mice expressed high levels of PD-1, PD-L1, PD-L2, CD39, CD73 and VISTA. Of those, only CD73 was downregulated by the MEK inhibitor trametinib indicating direct regulation by the oncogenic SHP2. Together with CD39, CD73 is a known ectonucleotidase that converts extracellular ATP to adenosine and thus induces an anti-inflammatory state. To test whether the checkpoint molecules affect T cell proliferation, we co-cultured wildtype (WT) T cells with Ptpn11D61Y/+ leukemic monocytes or granulocytes. Indeed, T cell proliferation was inhibited by leukemic monocytic cells. Proliferation could be restored by the CD39-inhibitor, POM-1. In contrast, inhibitors or monoclonal antibodies for CD73, PD1 and VISTA did not affect the inhibitory effect of leukemic cells on T cell proliferation. Summary/Conclusion: We conclude that the purinergic network is responsible for the immune escape of JMML cells and might be an attractive therapeutic target to prevent JMML relapse after HSCT. Other immune escape molecules such as PD1 and VISTA seem to play only minor roles in JMML. Keywords: T cell response, JMML, Immunosuppression